Selective estrogen receptor modulators (SERMs) are a class of compounds that bind to estrogen receptors (ERs) thereby inducing specific conformational changes in the receptors. SERMS can exert different effects in different tissues resulting from tissue-specific recruitment of coactivators (which enhance ER transcriptional activity) and corepressors (which repress ER transcriptional activity). SERMs are therefore distinguished from the so called “pure” estrogen receptor agonists/antagonists that uniformly activate or block estrogen effects independent of tissue type.
SERMS, by virtue of their effect on the estrogen receptor, are useful for treating a variety of disorders having an estrogen component. Many of these disorders are chronic disorders requiring long-term administration of the SERM. However, when administered over long periods of time, serious adverse effects have been observed, limiting the usefulness of these compounds. A significant advance in the art would occur if these SERMs could be administered to treat chronic estrogen receptor-mediated disorders.